The lab is interested in understanding molecular and cellular mechanisms underlying synapse formation and synaptic plasticity, and in the long term elucidating synaptic mechanisms underlying neuronal circuit function in animal behavior. We believe that these studies will provide fundamental insights into neural underpinnings for learning and memory, and will identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as epilepsy, Alzheimer's disease, depression and autism. Specifically, during the 2017 fiscal year, we have made following progress: For research Aim 1: we have successfully determined the role of GSG1L, a tetraspanning protein that binds to AMPARs, in the regulation of excitatory synaptic strength. Currently one manuscript for this work has been published in Nature Communications and another manuscript has been published in Journal of Neurophysiology. In addition, a manuscript about the role of FRRS1L, a novel and unexplored membrane protein in the regulation of AMPA receptor trafficking and function, is under review. For research Aim 2, we have identified a novel protein interacting with GABA-A receptors. Currently we have made substantial progress in determining the function of this protein in the regulation of GABAergic synaptic transmission. For research Aim 3: we have established a general molecular framework essential for GABAergic synapse development in hippocampus. Currently, a manuscript for this work is under revision. For research Aim 4, we have completed series of behavioral experiments in the mutant mice in which the majority of glutamatergic input onto midbrain dopamine neurons has been genetically inactivated. These experiments demonstrate that glutamatergic input onto dopamine neurons plays a specific and prominent role in behavioral processes that require high-level motivation. Currently, a manuscript about this work has been published in Molecular Psychiatry. Finally, during the 2017 fiscal year, we have collaborated with Dr. Katherine Roche group at NINDS, NIH to study the function of diseased-associated mutations in NMDA receptors. In addition, we have collaborated with Dr. Veronica Alvarez lab at NIAAA, NIH and Dr. Thomas Hnasko lab at UCSD to study the mutant mice lacking glutamatergic input onto dopamine neurons. We are also collaborating with Dr. Juan Song at UNC Chapel Hill to study the role of glutamate receptors in adult neurogenesis in hippocampus.